The present invention relates to a novel apparatus and method for surgical wound closure applications. Numerous medical applications exist where sealing of biological tissue is desired. U.S. Pat. No. 5,510,102 to Conchrum identifies a variety of applications including traumas of the liver, spleen, pancreas, lung, bone, etc.; cardiovascular and vascular applications, such as microvascular anastomoses, vascular grafts, intraoperative bleeding and aortic repair; and the like.
The described invention provides a means to remove the heparin from anticoagulated whole blood. A sample of blood intended for either diagnostic analysis or therapeutic use is drawn into a blood collection apparatus. The blood is exposed to a material that has an immobilized substrate that removes a negatively charged anti-coagulating agent, preferably heparin, from the ample. Blood drawn into and across the immobilized biomaterial will be de-heparinized, and therefore will be capable of clot formation.
The most prominent application is sealing of a vascular wound resulting from percutaneous entry, as is frequently encountered in angiography, angioplasty and atherectomy procedures. Percutaneous vascular access is typically required in the context of minimally invasive surgical procedures. These techniques are often used to reduce trauma to the patient. Reduced trauma typically translates to improved patient comfort, minimized procedural complications, and lower costs. The vessel accessed is typically the femoral or radial artery. Access involves placement of an introducer""s distal tip beneath the patient""s skin and through the arterial wall. To the extent possible, percutaneous access preserves the integrity of the tissue covering the artery. As a result, when the introducer is to be removed, the arterial access site is not exposed and the arterial wound is preferably closed without cutting down though the overlaying tissue to expose the site.
To accomplish hemostasis at the wound, numerous methods of post-introducer arterial closure have been tried. The prior art devices used in these methods may be broadly classified into two groups, those that mechanically achieve hemostasis and those that rely on clotted blood or components of blood to form all or a part of the hemostatic agent. By example, sutures, whether placed through an open surgical exposure of the artery or by means of a device designed to place sutures percutaneously are associated with mechanical methods, as these methods rely on mechanically closing the opening in the artery. The second group, those using clotted blood, include the predominant method of treatment, manual compression of the wound site. In this method, after the effects of any anti-coagulating drugs have worn off, an attendant applies compression to the wound site until a clot of sufficient strength has formed to stop bleeding. Alternatively, the attendant may apply any of various mechanical devices that will hold compression, such as a sand bag or a pneumatic clamp, until hemostasis is achieved.
Recently, a variety of devices have entered the market that aid in achieving hemostasis, even in the event of a patient whose blood is still actively anti-coagulated. These devices typically rely on mechanical methods such as sutures or upon various biologic substances, such as collagen and thrombin, that are known to induce clotting of blood even when anti-coagulating agents are present. The differences between the devices is largely in the delivery platforms used to position the biologic materials. Disadvantages of the prior art devices and methods vary depending on the method employed. Generally speaking, mechanical devices that deploy sutures are complex, expensive and technically difficult to employ. In addition, mechanical closure of the opening in an arterial wall can lead to a permanent restriction at that site as the diameter of the artery is reduced when the opening is pulled together, much like a purse string. Open vascular access closure by means of suturing requires the skill of a specialist, a vascular surgeon, a specialist not required for the procedure itself and, therefore, an additional expense. Suturing by means of a specially designed percutaneous device offers the advantage of a very rapid cessation of bleeding through the arteriotomy, but can lead to significant issues if the device malfunctions and becomes entangled in place. In addition, secondary bleeding, that from the capillary bed of the adjacent soft tissue, can be left untreated. This secondary bleeding can continue for extended periods, causing weeping at the wound site and potentially leading to infections.
Current methods which rely in whole or in part on clotted blood also suffer from significant drawbacks. The compression method requires that the patients blood return to normal clotting status by means of the natural metabolization of anti-coagulating drugs. This process can take several hours, a period during which the patient must remain in the vicinity of the catheterization lab with the procedural sheath still in place. The compression period, once it begins, can last for extended periods, sometimes more than two hours. This process is uncomfortable for the patient, often painful, and it is tedious for the attendant or attendants as well. In addition, hemorrhaging can occur if the site is not held properly or if the compression period is terminated too early. Also, due to the time involved, both in terms of attendant time and cath lab time, this process tends to be quite expensive.
The devices which have been designed to be used in association with methods which improve on devices using clotted blood, generally work in a more rapid manner, but not without additional risks. The biologic materials employed, collagen and thrombin, are very potent clot inducing substances, so much so that if they are inadvertently deployed into the artery rather than outside, adjacent to the artery, a limb or life threatening clot may form inside of the artery. This condition can be difficult to treat and, in the best of circumstances, require dramatic, extensive intervention. In addition, the biologic materials used are derived from animal sources, typically bovine, and, therefore, bring along other inherent risks associated with such sources. Included among these risks are allergic reactions and the possibility of contracting bovine spongiform encepholapathy (BSE), otherwise known as mad cow""s disease. The prior art devices are often technically difficult to use and their use can inhibit reaccess at the same site in situations where an additional procedure needs to be performed on the patient, such as in an emergency follow-up procedure. Transmission of infectious disease can also occur when the material used is manufactured from pooled human blood as reported in Opth. Surg., 3:640 (1992). Autologous preparations like fibrin glue, as described in U.S. Pat. No. 5,674,394 to Whitmore, are well known, but significant preparation, with the associated labor and material costs, is required and typically an additional thrombin material is still required at the wound site.
Despite the need for a device and a method which overcomes the limitations of the prior art, the prior art devices and methods have failed to adequately address the needs for a rapid and efficacious method of closing vascular and other wounds. Accordingly, it will be appreciated that there is a need for an efficient way of closing wounds. The present inventions provide advantages over the prior devices and the prior methods used to close wounds, and also offer other advantages over the prior art and solve other problems associated therewith.
The present invention provides improved methods of creating hemostasis or control of bleeding at the site of wounds, particularly wounds created in arteries during procedures employing percutaneous access. The invention preferably includes the steps of acquiring an aliquot of a patient""s blood, i.e., autologous blood, removing a negatively charged anti-coagulating agent, preferably heparin, from the blood, and preferably initiating the blood""s natural clotting cascades and transporting the thus treated blood to the site of the wound where the clotting cascade will be completed producing a clot at the wound site that will create a condition of hemostasis. The invention further provides a clotting cascade initiation apparatus including a substantially enclosed sterile containment chamber within which an aliquot of blood fluid, either autologous or from donor sources, can be received and retained. In preferred embodiments, the sterile containment chamber further includes a heparin binding agent which will bind heparin and remove it from the blood fluid. In further embodiments the containment chamber will also include a procoagulating agent, wherein a clotting cascade can be initiated when the blood fluid is accepted into the sterile containment chamber. Once the clotting cascade is initiated, the blood fluid is returned to the wound within the patient such that the clotting cascade can be completed and a clot can form within the wound. The invention further provides a method of using the clotting cascade initiation apparatus of the present invention to close a wound preferably including the step of drawing an aliquot of the patient""s blood fluid. The invention further provides a method of using the clotting cascade initiation apparatus, preferably including providing a kit, preferably including providing a preferred sterile containment chamber and a vascular sheath for drawing an aliquot of blood fluid, preferably autologous blood fluid from the patient, and said blood fluid to a wound site within a patient once a substantial percentage of any heparin within the blood fluid drawn into the sterile containment chamber has been removed from the blood fluid within the sterile containment chamber, and once the clotting cascade has been initiated within such blood fluid. The invention further provides a method to initiate the natural intrinsic clotting cascade mechanism of human blood, wherein the intrinsic clotting cascade mechanism can be initiated when the blood is accepted into the sterile containment chamber, this blood with the intrinsic clotting cascade mechanism being useful when delivered to the wound site from the apparatus, where the natural extrinsic clotting mechanism is activated. This blood, with both the natural intrinsic and extrinsic clotting mechanisms being activated, then completes the clotting cascade process once delivered to the wound site, thus forming a clot of sufficient strength to stop blood flow from the wound site. Alternate embodiments of the invention provide methods to inactivate or remove the anti-clotting drug heparin by binding the heparin and removing it from the blood. The invention provides the methods to activate the natural intrinsic clotting cascade mechanism by means of activating blood factor XII by exposure to sufficient, specific biomaterial surface contact; and blood factor VIII by way of introducing sufficient mechanical shear. The invention further provides the method to activate and benefit from the natural extrinsic clotting cascade mechanism by means of blood factor VII activation from wound tissue contact. The described invention provides a means to remove the heparin from anticoagulated whole blood. The blood is exposed to a material that has an immobilized substrate that removes a negatively charged anti-coagulating agent, preferably heparin, from the sample. Blood drawn into and across the immobilized biomaterial will be de-heparinized, and therefore will be capable of clot formation.
It is believed that the present invention offers significant advantages over the prior art methods and devices. The use of naturally clotted blood as a hemostatic agent is the way nature intended wounds to be sealed and is the means proven most safe and reliable in standard hospital practices. By substantially removing the anti-coagulating agent heparin from blood, whether autologous or from donor sources, the blood is returned to a condition where natural clotting activities can occur and be manipulated. By controlled and measured initiation of the intrinsic clotting cascade mechanism, blood factors VIII and XII can be activated, thus producing a blood sample that will, in a predictable time frame, advance towards a completed clot. This process is further enhanced when the blood sample is returned or placed in the body in the soft tissue adjacent to the arteriotomy. Contact of such de-heparinized blood, while it is still in a fluid phase, with the exposed surfaces of the tissue will initiate the extrinsic clotting cascade mechanism as controlled by blood factor VII. This now fully treated blood, preferably with virtually all traces of heparin inactivated or removed, and both the intrinsic and extrinsic pathways activated, whereby preferably blood factors VII, VIII and XII have all been activated, will quickly transform from fluid phase blood to a solid phase blood clot of sufficient strength and quantity to create a condition of hemostasis. In the event that the activated blood is inadvertently deployed to one degree or another into the accessed blood vessel, rather than just adjacent to it, the blood deposited inside the vessel will not progress to form a clot, but merely mixes with the blood within the vessel and dissipates in the blood. The treated blood within the wound, however, will complete the clotting process and fibrin clot will form to close the wound and stop the flow of blood through the wound.
As used herein, the following terms have the following meanings: xe2x80x9cBlood fluidxe2x80x9d means whole blood or a fluid containing natural components of whole blood, whether derived from whole blood, whole blood extracts, or products of ex vivo cell cultures, the blood fluid containing sufficient blood components to enable a portion of the blood fluid to clot subsequent to the initiation of a clotting cascade; xe2x80x9cClotting cascade(s)xe2x80x9d means a sequential series of chemical, proteolytic/enzymatic reactions naturally occurring which, if not inhibited or interrupted, result in clot formation; xe2x80x9cClotxe2x80x9d means a solidified mass of blood fluid having most of the available fibrin polymer cross-linked; xe2x80x9cBiocompatiblexe2x80x9d means an agent is regarded by the regulating government body to be acceptable for use in the human body; xe2x80x9cProcoagulantxe2x80x9d means any process, activity, material or substance that serves to initiate, continue or accelerate a clotting cascade; xe2x80x9cAnti-coagulating agentxe2x80x9d means a component capable of preventing blood fluid clot formation. All patents, patent applications, and references cited herewith are hereby incorporated by reference.
These and various other advantages and features of novelty that characterize the present invention are pointed out with particularity in the claims annexed hereto and forms a part hereof However, for a better understanding of the present invention, its advantages and other objects obtained by its use, reference should be made to the drawings, which form a further part hereof and to the accompanying descriptive matter, in which there is illustrated and described preferred embodiments of the present invention.